通过开发和应用基于生理学上的4-tert-octylphenol毒动力学模型来评估人类的风险
Ji-Hun Jang1, Seung-Hyun Jeong2
1College of Pharmacy, Sunchon National University, 255 Jungang-ro, Suncheon-si, Jeollanam-do, 57922, Republic of Korea.
Environmental pollution (Barking, Essex : 1987)
|July 25, 2024
概括
一个新的生理学基础毒动力学 (PBTK) 模型量化了人类暴露于4-tert-octylphenol (4-tert-OP) 的风险. 该模型有助于评估不同人群的风险,揭示不同暴露水平,并强调需要持续进行四级OP监测和管理.
科学领域:
- 毒理学 毒理学 毒理学
- 环境健康 环境健康
- 药理动力学 药理动力学
背景情况:
- 4-tert-octylphenol (4-tert-OP) 是一种生态危险物质,在环境中广泛存在.
- 目前评估人类暴露于4-tert-OP风险的工具有限.
研究的目的:
- 开发一个4-tert-octylphenol (4-tert-OP) 的生理基毒动力学 (PBTK) 模型.
- 使用PBTK模型对不同人群中的4-tert-OP进行定量风险评估.
主要方法:
- 建立并验证了使用雄性大鼠毒动力学数据为4-tert-OP的PBTK模型.
- 通过反向剂量计将老鼠模型推广到人类,并通过反向剂量计估计人类参考剂量.
- 将生物监测数据应用于人类PBTK模型,以计算外部暴露和安全边际.
主要成果:
- 该PBTK模型准确地解释了毒动力学数据,并预测了丸中的4-tert-OP水平,与男性生殖毒性相关.
- 系统性和生殖性毒性的估计人体参考剂量分别为0.16和1.12毫克/千克/天.
- 在不同人群中,平均外部4-tert-OP暴露量差异很大 (0.04-66.24毫克/公斤/天),风险从安全到令人担忧.
结论:
- 开发的PBTK模型为量化评估4-tert-OP对人类的风险提供了一个强大的工具.
- 在4-tert-OP暴露的显著变化需要持续的全球监测和风险管理策略.
- 该研究提供了对4-tert-OP人类暴露和风险评估的关键科学见解.
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